Toll-like receptors (TLRs) are proteins on the outside of certain cells that identify and help destroy disease-causing organisms (called pathogens) that have entered the body. They are present in areas of the body that are frequently exposed to outside substances such as the skin, nose, eyes, mouth, or gastrointestinal tract.

TLRs are part of a larger group of proteins called pattern-recognition receptors (PRRs). These proteins are key components in the body's innate immune system. This branch of the immune system is the body's first line of defense against foreign substances trying to enter the body and cause illnesses. All humans are born with innate immunity. This type of immune response is both immediate and nonspecific. In other words, immune cells involved in innate immunity are not specific to just one type of foreign substance. Instead, the immune cells can recognize and destroy a wide range of pathogens.

PRRs, including toll-like receptors, are constantly surveying the body for pathogens, such as bacteria and viruses. They are able to recognize disease-causing organisms (such as bacteria or viruses) by their pathogen-associated molecular patterns (PAMPs). PAMPs are cellular patterns that are shared by a large group of organisms. Since these patterns are different than human cells, they will not mistakenly attack body cells.

TLRs are named after a closely related receptor in the fruit fly, called a toll receptor. Both the human TLRs and the fruit fly toll receptors stimulate the immune response, which leads to the destruction of the invading pathogen.

Since 1994, researchers have identified 11 different types of TLRs in humans and 13 in mice. Researchers believe that each type of TLR can detect the cellular patterns of different groups of organisms. In other words, each type of TLR is able to identify different groups of harmful microbes.

TLRs are predominantly found on the outside of antigen presenting cells (APC), including neutrophils, macrophages, and dendritic cells. When the TLR identifies a foreign invader, the APC engulfs it. The APCs then break down the pathogen so that other immune cells (such as T-cells and CD4 cells) can identify and destroy the harmful invader. In addition, TLRs have been found in a wide range of body tissues, including the adrenal glands, liver, testis, spinal cord, lungs, thymus gland, and trachea. This suggests that most cells in the body express TLRs to help fight against diseases and infections.

Toll-like receptors are an important part of the body's innate immune system, also called the natural immune system. These receptors are part of the body's first line of defense against harmful substances that enter the body.

The receptors, located on the outside of immune system cells, are constantly surveying surrounding cells and tissues for pathogens. Each type of TLR is able to recognize a wide range of pathogens. This is because TLRs recognize pathogens based on their pathogen-associated molecular pattern (PAMP). Since large groups of microbes share the same PAMPs, a single TLR is able to recognize many different invaders.

Toll-like receptors (TLRs) become activated once they identify and bind to a foreign substances that enter the body. Once stimulated, the TLRs activate signaling pathways that trigger an immune response. This immune response eventually leads to the expression of many antimicrobial genes that are necessary for immune cells to destroy the invading substances. TLRs also trigger the release of inflammatory chemicals called cytokines.

In 1997, researchers discovered that a specific TLR, called TLR4, can activate certain genes needed to initiate an adaptive immune response. Adaptive immunity is a type of protection that develops over the course of an individual's life. Adaptive immunity involves the development of immunoglobulin antibodies that respond to specific foreign substances that enter the body. When individuals are exposed to certain foreign invaders, they develop antibodies against the pathogens. Then, if the same substance enters the body in the future, the body is then prepared to respond quickly because the antibodies are already developed. The antibodies detect and bind to foreign substances that enter the body signaling other immune cells to destroy it. However, it remains unclear exactly how TLR4 is involved in adaptive immunity.

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.